The epigenetic and transcriptional events controlling the differentiation of antibody- secreting plasma cells (PCs) from activated B cells remain unclear. Furthermore, though memory B cells and naive B cells in the marginal zone (MZ) of the spleen are known to generate PCs faster than the bulk of naive B cells, how PC inductive signals integrate with other processes such as cell division to drive PC differentiation in distinc B cell subsets is unknown. The main goals of this R21 application are to understand how epigenetic modifiers control the kinetics of early PC differentiation for MZ and memory B cells and the role of cell division in these processes with an emphasis on the regulated expression of the PC-required transcription factor Blimp1. To this end we will: 1) Define the role of cell divisin in PC differentiation, and 2) Define the epigenetic regulation of the Blimp1 locus upon B cell activation and selection. These studies will enhance knowledge of the processes underlying the generation of all PCs including pathogenic PCs secreting self-reactive antibodies.